Clinical Aspects of Buprenorphine Therapy in the HIV Primary Care Setting


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In this webinar, clinicians from two Ryan White clinics with successful buprenorphine programs describe what buprenorphine is, how it works, what opioids do to the brain, how buprenorphine differs from methadone, important drug-drug interactions, the concept of precipitated withdrawal and how to recognize it, how to determine patient eligibility, and clinical aspects of working with opiod-addicted people living with HIV.

Presenters Pamela Vergara-Rodriguez, MD, (CORE Center in Chicago), and Jacqueline Tulsky, MD (University of California at San Francisco and San Francisco General Hospital), also describe the challenges and successes of the SPNS buprenorphine projects at their institutions.

Visit the Integrating HIV Innovative Practices webpage to learn more about integrating buprenorphine into HIV primary care settings and to access additional training materials.

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  • Opioids Attach to Opioid ReceptorActivation of the μ receptor by an agonist such as morphine causes analgesia, sedation, slightly reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils) and decreased bowel motility often leading to constipation. Some of these side effects, such as sedation, euphoria and decreased respiration, tend to lessen with continued use as tolerance develops. Analgesia, miosis and reduced bowel motility tend to persist; little tolerance develops to these effects.
  • ASAMAddiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in the individual pursuing reward and/or relief by substance use and other behaviors. The addiction is characterized by impairment in behavioral control, craving, inability to consistently abstain, and diminished recognition of significant problems with one’s behaviors and interpersonal relationships. Like other chronic diseases, addiction can involve cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death.Addiction is defined as a behavioral syndrome characterized by the repeated, compulsive seeking (psychological dependence) or use of a substance despite adverse social, psychological, and/or physical consequences, along with the physical need for an increased amount of a substance as time goes on to achieve the same desired effect. Addiction is often (but not always, as with an addiction to gambling) accompanied by tolerance, physical dependence, and withdrawal syndrome.The American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, recognizes these definitions below as the current accepted definitions. Addiction:Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. II. Physical Dependence:Physical dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. III. Tolerance: Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. Summary:Addiction is uncontrollable compulsive behavior caused by alterations of parts of the brain from repeated exposure to high euphoric responses.Many of you ust of gotten very excited when I metnioned the word sex thinking I would be talk about sex addiction today but in fact I want to clarify that I am acutally talking about drug addiction
  • Long-term or high dose use of opioids may also lead to additional mechanisms of tolerance becoming involved. This includes downregulation of mu opioid receptor gene expression, so the number of receptors presented on the cell surface is actually reduced, as opposed to the more short-term desensitisation induced by β-arrestins or RGS proteins.[15][16][17] Another long-term adaptation to opioid use can be upregulation of glutamate and other pathways in the brain which can exert an opioid-opposing effect and so reduce the effects of opioid drugs by altering downstream pathways, regardless of mu opioid receptor activation.[18][19]
  • In 2010, among adult and adolescent males diagnosed with HIV infection MSM is the largest risk category, but 7% were attributed to injection drug use.and 4% attributed to male-to-male sexual contact and injection drug use. In women and 14% were attributed to injection drug use.  
  • Clinical Aspects of Buprenorphine Therapy in the HIV Primary Care Setting

    2. 2. OPIOIDS AND HIV  You may know that…  Injection drug use (IDU), either directly or via sexual contact with an IDU partner, accounts for one-third of the cumulative estimated AIDS cases in the U.S.
    3. 3. OPIOIDS: SHOCKING FACTS  Dependence/abuse of pain relievers ranked second (after marijuana) among illicit drug use in the U.S.  Prescription opioid abuse may be proportional to the number of opioid prescriptions written.1  “[B]etween 2004 and 2008, emergency department visits involving oxycodone, hydrocodone, and methadone increased 152%, 123%, and 73%, respectively.”2  Mortality among illicit opioid users has been estimated at 13 times that of general population. 1. Lum P, Little S, Botsko M, et al. Opioid-prescribing practices and provider confidence recognizing opioid analgesic abuse in HIV primary care settings. JAIDS. 2011; 56(Suppl 4): S91-7. 2. Lum P, Tulsky JP. The medical management of opioid dependence in HIV primary care settings. Current HIV/AIDS Reports. 2006; 3(4): 185-94.
    4. 4. SPNS BUPRENORPHINE INITIATIVE Funded between 2004-2009  Key findings from initiative:        Providers and patients were overwhelmingly satisfied with results Improved HIV medication adherence and viral load. Reduced risk behaviors. Improved overall health outcomes. Patients felt incredibly lucid and stated improved quality of life and social functioning. To share training materials and best practices SPNS has launched the “Integrating HIV Innovative Practices” (IHIP) project.
    5. 5. To access training resources, visit:
    6. 6. TODAY’S AGENDA Dr. Vergara-Rodriguez, CORE Center in Chicago  Dr. Tulsky, San Francisco General Hospital   Discussing  Sarah Cook-Raymond  Discussing  clinical aspects to care Q&A qualifications to get started
    7. 7. Clinical aspects of integrating buprenorphine into the HIV primary care setting Pamela Vergara-Rodriguez The Ruth M Rothstein CORE Center HRSA HIV/AIDS Bureau: SPNS
    8. 8. Opium is an extract derived from the seedpods of poppies OPIOIDS Opioids stimulate the release of dopamine and produce pleasurable feelings Natural Semi-synthetic Synthetic Morphine Heroin Codeine Oxycodone Hydrocodone Buprenorphine Methadone Fentanyl Propoxyphene Diphenoxylate Hydromorphone
    9. 9. What are opioids? MUopioid Receptor OPIOID MUopioid Receptor OPIOID Receptors Mu Kappa Delta (+) Activity at BRAIN MU BUPRENORPHINE Receptors leads to Euphoria Sedation ↓ BP ↓RR Constricted Pupils Itching (+) Activity MU Receptors in the intestinal ANALGESIA tract leads to nausea and constipation
    10. 10. ADDICTION •Addiction is a behavioral syndrome where drug procurement and use dominate the individual’s motivation and where the normal constraints on behavior are largely ineffective…… ……may or may not be accompanied by physical dependence on the drug. Food PORN Video Gamble Shop TV Exercise Sex Internet Pharmacologically Active Substances “DRUGS”
    11. 11. why are opioids they so addictive? Opioid Addiction • Opioids attach to opioid receptors in the brain – – – – High (Intoxication) Dependence Analgesia Tolerance • Opioids stimulate the release abnormal amounts of dopamine and produce pleasurable feelings beyond what is normal – Normal pleasures become nonpleasurable (anhedonia) Opioid Physiologic Dependence • Produces Tolerance – Tachyphylaxis – Need more drug to prevent withdrawal – Need more drug to get euphoria • Produces Withdrawal – – – – – severe dysphoria, depression sweating, rhinorrhea nausea, vomiting loose stools severe fatigue, pain Opioid Antagonists/Partial Agonists can also produce withdrawal when given to an opioid intoxicated patient (naltrexone, naloxone, buprenorphine)
    12. 12. What is buprenorphine? How does it work? What's the safety profile? • agonist/antagonist (partial agonist) at the Mu Receptor • attaches to the receptor very strongly – pushes off other opioids • less respiratory depression • little Euphoric Effect • limited maximal positive effect on the receptor (ceiling effect)
    13. 13. How does buprenorphine differ from methadone? • Graph Buprenorphine Schedule 3: low likelihood to induce tolerance or addiction Increased safety because of ceiling effect on respiratory depression Naloxone reverses the effect of buprenorphine slowly Methadone Schedule 3:
    14. 14. How do you identify which patients have opioid abuse issues? • Universal Screening – (patient reports misuse, abuse, dependence) • Patient presents intoxicated • Patient presents in Withdrawal • Provider becomes aware thru a third party – Pharmacist, another provider, prescription monitoring • Patient presents with drug seeking behavior
    15. 15. How did you identify which patients may be a good candidate for buprenorphine? Good candidate • Opioid Dependent. Actively using • Recent Opioid Dependence with cravings • Good Engagement/ Good Attachment Less favorable candidate • On Methadone over 40mg • Known Diversion • Misuse/Abuse/Dependence of CNS depressants: Alcohol/Benzodiazepines/ Other tranquilizers • Unable to use sublingual formulations • Cognitive Deficits • Active Psychiatric Illness • ???Poor Compliance???
    16. 16. What is the process for buprenorphine administration: induction, PRE-INDUCTION INDUCTION STABILIZATION STABILIZATION Day-2 Day 1 Withdrawal Assessment Day 2 DAY 3 Medical History Medications LABS Pregnancy Test UDS Observe sublingual administration 1 tablet Observe sublingual administration 1 tablet Observe sublingual administration 1 tablet Education Withdrawal Specifics RX: 1 tab home RX: 1 tab home RX: 1 week supply Daily Counseling Daily Counseling Daily Counseling Alcohol and Drug Screening and Assessment Assessment for Dose increase
    17. 17. Buprenorphine Induction •COWS – Clinical Opioid Withdrawal Scale to assess severity of withdrawal (score: 5-12=mild; 13-24=moderate; 25-36=moderately severe; more than 36 = severe withdrawal) •Administer 4mg (1/2 tablet) •Observed for 30 minutes, administer COWS again •Administer 4 mg •Usually relief of withdrawal should begin within 3045 minutes •Take home medication with instructions
    18. 18. What is the process for buprenorphine, and maintenance? STABILIZATION MAINTENANCE Week 2-4 Month 2-12 Assessment for symptoms of underdosing Q month Assessment Check Clinical Stability, dose UDS: Weekly UDS: Every 2-4 weeks RX: weekly supply RX: 2-4 week supply Counseling Week 2: 1-2 days/week Week 3 &4 : Once weekly Counseling Once Every 2-4 weeks Symptoms of Under-dosing: Significant Craving, Pain issues, withdrawal symptoms, positive opioid toxicology
    19. 19. What was your experience with buprenorphine? What you Need: • Staff with right Attitude • Cohesive Treatment Team • CLEAR RULES • Ongoing Patient Education • Reinforcement of Good Behavior • Ongoing Provider Education/Communication What you don’t need • Judgment • Splitting • Patient RULES • One Time explanation • Punishment • Isolation of Treatment Team
    20. 20. Staff Providers Service Description Provider /Prescriber (MD) Buprenorphine Induction Opiate withdrawal evaluation and Buprenorphine induction Administrator Office Management Correspondence, ordering supplies, budget oversight, documentation review Clinical Coordinator Social Services Referrals for housing, legal services, food pantry, clothing, ID cards Substance Abuse Screening and Referral Refer to BUP Program or other outside agencies Substance Abuse Group Individual counseling and once weekly BUP group : 1 hour Buprenorphine Induction Manage follow-up induction protocol
    21. 21. What information do you wish you knew at the onset? • It’s not Magic • Antidepressant effect: Buprenorphine has kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety • Predictors of drop-out: Separation from spouse, poor family/social functioning, less education, female, psychiatric dysfunction • Patient Education is KEY
    22. 22. Neurobiology of Withdrawal and Induction • As opioids detach from the receptors, people experience withdrawal and CRAVING Brain without Opioids Brain After BUP Opioid receptors must be empty i.e., patient must present in withdrawal for induction Induction Buprenorphine will occupy the empty opioid receptors
    23. 23. Other clinical issues • Behavioral Treatment must remain the focus of treatment • Other drug dependences must be addressed • Contracts: Agreement • Addressing slips/relapses • Addressing Diversion • Easier to Hold Bup or split Bup and treat acute Pain as opposed to adding short acting opioids for pain
    24. 24. SPNS Buprenorphine Training Jacqueline Tulsky, MD UCSF Professor of Medicine SFGH Positive Health Program Opioid Treatment Outpatient Programs
    25. 25. OA’s story 39-yr-old w/ HIV and Hep C suppressed on ART, fairly adherent and is bonded to his primary care provider  In and out of jail and prison directly/indirectly related to heroin addiction  Multiple methadone detox episodes, struggles with getting in to dose and craving and rarely finishes detox  In jail heard about a “new” drug your own doctor could prescribe for opioid dependence
    26. 26. OA’s story continues  Screens eligible for buprenorphine/naltrexone (bup/nx) at new program in HIV clinic  Rocky induction, but quickly settles into weekly, then monthly refills with counseling sessions  Overall benefits  Out of jail for 5 years, works some, family connected  Struggles with depression  Very engaged in HIV care
    27. 27. Background  Moving Mountains: Integrating HIV care and Addiction treatment  Part of HRSA-funded Buprenorphine Initiative at 10 sites from 2004-2009
    28. 28. Injecting Drugs & HIV/AIDS Over 1.15 million HIV cases in the US through end 2009 Cases attributed to Injection Drug Users (IDU): • • All reported cases through 2008 = 17% New cases in 2009 = 9% Overall trend toward decrease in IDU-related cases because of effective interventions to stop transmissions CDCP, Atlanta; HIV/AIDS Surveillance Report, 2012 (22)
    29. 29. Q. Why bup/nx? A. The opioid treatment gap  In 2006 NSDUH estimated 323,000 heroin dependent persons in the US  In 2009 the gap between those needing opioid treatment and those getting treatment was over 600,000 persons*  5 states with no methadone programs *Buprenorphine Q&A :NIDA/NIH May, 2009
    30. 30. Q. Why bup/nx? A. Patient safety and preference  Less arrhythmia risks through QTc prolongation with bup/nx compared to methadone  Trend of interactions are to lower bup/nx which can be addressed with dose adjustment.  Less sedation, less restrictions than methadone  Comprehensive care from primary provider AIDS Monograph, 2012 BHIVEs Investigators
    31. 31. Q. Why bup/nx? A. Provider perspective  Wanted to address important factor in HIV care  Monitor drug use  Address barrier to adherence  Take advantage of good patient-provider relationship  Exciting/challenging new skill/service for providers and the health care system AIDS Monograph, 2012 BHIVEs Investigators
    32. 32. How to determine who is eligible? “OA screens eligible for bup/nx”  Known opioid addicted patients approached by providers. Soon some self referral.  Social workers/nurse with addiction background screened patients with a protocol for:  Polysubstance use with benzos and ETOH  Chronic opioid pain meds  Need for more structure in drug treatment
    33. 33. Drug-Drug Interactions? CYP3A4 Effects  Not a significant issue except for CNS active meds/drug used w/o close monitoring  Many drugs decrease the drug concentration of bup/nx,  On initial induction not really an issue  Monitor for withdrawal with protease inhibitor drugs, some antibiotics (ex: rifampin, ciprofloxacin) (Also see the IHIP training manual’s drug-drug interaction chart:
    34. 34. Challenge of Induction OA has a “rocky induction” because of initial precipitated withdrawal. Was afraid of full withdrawal and didn’t completely believe bup/nx would help. Had used the day before, but only a” small amount”, not in full withdrawal. Asked to come back later in the day, but with test dose had Had vomiting/diarrhea/cramps and “fluid bath” after initial test dose. Additional dose an hour later and felt better Given dose to take that night and came back next day. Precipitated withdrawal a risk due to the partial agonist/antagonist properties of buprenorphine How to prevent: SOAP note format w/ COWS
    35. 35. Classic Precipitated Withdrawal A risk due to the partial agonist/antagonist properties of buprenorphine “Narcan effect” How to prevent: SOAP note format w/ COWS
    36. 36. Induction SOAP Note Subjective Data  Elicit symptoms of opioid withdrawal  Include pt’s rating of sx (mild/moderate/severe). Objective Data  Document signs of opioid withdrawal (COWS)  Signs of intoxication? Assessment  In opioid withdrawal? YES or NO.  Include severity (mild, moderate, severe) based on COWS score. Must have at least mild signs of withdrawal and COWS >5 before test or first dose.
    37. 37. Induction SOAP Note (cont.) Plan NO:  Pt appears intoxicated or no signs of withdrawal. Reschedule for a later date or time.  Counsel on the importance of presenting in some withdrawal for a more comfortable overall induction.  Address fears YES:  Begin bup/nx dosing  Titrate to target dose per clinical guidelines protocol.
    38. 38. Models of Bup/n Rx Integration Covering screening, counseling, education, monitoring induction & stabilization, ongoing contact role Sound like like HIV or diabetes care? Primary Care: BUP/nx prescribed by the HIV PCP Relay: Off or On Site by Addiction Specialist May be opportune to do induction outside of regular PCP clinc.
    39. 39. Consideration for Providers  New training and skills  Your colleagues are not trained for addiction • Some eagerly seek out, others avoidant • Finding the Champion in your group  New patients • May bring drug users to primary HIV care • Comfort level working with drug users • Insurance and med coverage issues
    40. 40. Unexpected Outcomes? Double or Nothing phenomenon  The patient benefits by both better HIV and substance use outcomes or  The patient disengages from both drug treatment and HIV care, when one becomes difficult
    41. 41. Has integration worked? YES  For some patients stabilized an aspect of his health care within the PCP relationship  PCPs can really addresses drug use barriers to HIV care  Much more interest by junior faculty than more senior
    42. 42. Has integration worked? YES, but….  Patients still have multiple physical, mental health and sometimes ongoing addiction issues  Bup/nx has added a important tool, but does not directly address other drugs of abuse i.e stimulants  One or two “practice partners” plus an engaged nurse and pharmacy group have been enough to support about 25 patients
    43. 43. Conclusion  Bup/nx allows for integrated care to patients with HIV and opioid dependence  The model is similar to other chronic diseases for induction and maintenance  Word of mouth among the patients is good, and should be encouraged.
    44. 44. HOW DO I GET STARTED?
    45. 45. PRESCRIBING BUPRENORPHINE  Who can prescribe buprenorphine?   What training is necessary?     Qualifying physicians Required board specialty, or 8 hours of approved training To access qualifying physician trainings, visit:,,, or Notify SAMHSA for Waiver to treat  See diagram on next slide  If approved, receive notice and DEA registration number  1st year=maximum treatment of 30 patients per authorized physician. After 1st year, may apply for additional waiver to treat up to 100 patients.
    46. 46. TREATING PATIENTS: ONLINE REQUEST FORMS  To access and email notifications, visit: r_online=ONLINE.  To access an online form to fax or mail in, visit: r_online=PREFILLED OR and send to the contact information below: Substance Abuse and Mental Health Services Administration Division of Pharmacologic Therapies Attention: Opioid Treatment Waiver Program One Choke Cherry Road, Rm 2-1063 Rockville, MD 20857 Fax 240-276-1630 Phone 1-866-287-2728 (1-866-BUP-CSAT)  (To learn more about increasing patient limits, visit:  SAMHSA. Buprenorphine: how to obtain a waiver. n.d. Available at: Accessed December 9, 2011.
    47. 47. DIAGRAM OF WAIVER PROCESS (To learn more about waiver qualifications, visit
    48. 48. COUNSELING SERVICES  Physicians either need to offer counseling services or have formal referral systems in place to link patients undergoing opioid treatment to counseling.  To view a grantee example of referral procedures, visit phine_ProgramProtocols.pdf.
    49. 49. OTHER CONSIDERATIONS Confidentiality: Records for substance abuse treatment have stricter standards than traditional medical records. Safety: Buprenorphine must be stored in securly locked cabinet. Any theft must be reported to DEA.
    50. 50. IHIP RESOURCES  All of this information is available in detail on the IHIP site:
    51. 51. Q&A